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Microscopy, The immune system

Cells have a skeleton, and a very clever way of organising it

Just like humans, each of our cells have a skeleton in order to maintain their shape. Up until recently, we didn’t have the ability to see their skeleton in great detail. But with new technology creating ever-more powerful microscopes, we can now see the skeleton and the patterns it creates to maintain the cell’s structure. In this blog post, Dr Marco Fritzsche discusses his recent paper published in Nature Communications in collaboration with Prof Christian Eggeling and Prof Eric Betzig, researching exactly how the skeleton of a cell is organized.

One fundamental question in biology is how cellular structures are organized in space and time. While cell biology has gained a good understanding of important processes, including structural and functional knowledge of many molecules, the organization underlying the cell skeleton remains unclear. A better understanding of this process will help us unravel how cells can rapidly respond to changes in their environment – with particular relevance for the immune system.

There are two fundamentally different mechanisms that are known to generate structures in cells: self-assembly and self-organization. Self-assembly involves the physical association of molecules into a balanced structure that is stable over time with no need for additional energy. In contrast, self-organization requires the collective action of interacting molecules that are not in energy balance. This means that in order for the self-organised structure to be maintained, there needs to be a constant input of energy. A range of theoretical considerations and cell-free experiments have demonstrated that cell skeleton molecules (called actin) can employ such self-organization in the form of actin patterns, but it is yet to be demonstrated directly in a cell.

Our group (www.bpi-oxford.com), in collaboration with Prof Christian Eggeling and Prof Eric Betzig (Noble Laureate 2014) have now demonstrated, for the first time, how the actin cytoskeleton employs mechanisms of self-organization to dynamically generate different actin patterns in a cell. We used state-of-the-art super-resolution microscopy to monitor these transitions over time in living cells. We demonstrated that when cells stick to a surface, an active coarsening process naturally leads to the formation of skeleton patterns called actin vortices. Unexpectedly, pattern dynamics were primarily driven by one specific central actin complex, the Arp2/3 complex, but not by movement (myosin) proteins. This is in contrast to what had been theoretically predicted and observed in vitro. We also made measurements of cell mechanical properties and cell membrane fluidity, which indicated that cell skeleton patterning alters the cell’s membrane architecture but occurs at constant elasticity. This means that self-organizing actin patterns may allow cells to adjust their membrane architecture without affecting their overall mechanical properties. These observations support the idea that actin patterns may mediate the dynamic organization of the cellular membrane – which, for example, may allow immune cells to effectively coordinate their immune receptors during an immune response.

Actin Aster

An actin aster – a star shaped pattern formed by actin

With advances in technology allowing us to study cell processes that have never been seen before, we now have a greater insight into how cells organise themselves on a structural level. Future investigations by our team will extend this research by focussing on characterising the skeleton in highly specialised cells, such as immune cells, which require very specific and energy-consuming reorganizations of the actin cytoskeleton in order to defend our body from infection.

This post was edited by Lauren Howson.

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